The objective of this study is to elucidate the cellular and molecular mechanisms of neoplastic development and to understand how environmental agents influence the progression of normal cells to malignancy. The specific aims of the research are: (1) identification of preneoplastic states during neoplastic development; (2) determination of the role of somatic mutation in a multi-stage model of carcinogenesis; (3) elucidation of whether benign neoplastic cells progress to malignant cells; and (4) understanding the biochemical basis of cellular invasion. The studies involve model systems of oncogenesis which employ fibroblasts and epithelial cells in culture.